Selective retina therapy: toward an optically controlled automatic dosing

Abstract

Selective retina therapy (SRT) targets the retinal pigment epithelium (RPE) with pulsed laser irradiation by inducing microbubble formation (MBF) at the intracellular melanin granula, which leads to selective cell disruption. The following wound healing process rejuvenates the chorio-retinal junction. Pulse energy thresholds for selective RPE effects vary intra-and interindividually. We present the evaluation of an algorithm that processes backscattered treatment light to detect MBF as an indicator of RPE cell damage since these RPE lesions are invisible during treatment. Eleven patients with central serous chorioretinopathy and four with diabetic macula edema were treated with a SRT system, which uses a wavelength of 527 nm, a repetition rate of 100 Hz, and a pulse duration of 1.7 μs. Fifteen laser pulses with stepwise increasing pulse energy were applied per treatment spot. Overall, 4626 pulses were used for algorithm parameter optimization and testing. Sensitivity and specificity were the metrics maximized through an automatic optimization process. Data were verified by fluorescein angiography. A sensitivity of 1 and a specificity of 0.93 were achieved. The method introduced in this paper can be used for guidance or automatization of microbubble-related treatments like SRT or selective laser trabeculoplasty.

Selective Retina Therapy

“…Neither reference grids for DME nor well localized circles or patterns in CSR treatment can be placed due to lack of visual feedback. On the other hand, with respect to proper energy dosage, studies showed a strong inter-and intraindividual variation of the necessary pulse energies for comparable RPE effects [63,64]. Even with titration at the arcades, angiography after treatment is required to ensure RPE defects due to the variability of the absorption.…”

“…Typically, an annular shaped piezoelectric ultrasonic transducer is embedded in the contact lens, which is used anyway for laser treatments utilizing a laser slit lamp [73]. Figure 11.7b (blue curves) show such transients when using SRT at low radiant exposures [64]. Since the pressure is proportional to the pulse energy, all transients are almost identical when normalizing on the energy (Fig.…”

“…As long as the irradiation takes place in the therapeutic window with radiant exposures slightly above the MBF threshold that only causes small separated microbubbles, a selective cell damage without any adverse effects to the photoreceptors and the choroid has been proven in multiple clinical trials [45, 46, 48, 51, 52, 54, 55, 57-59, 61, 65-67]. MBF and blood-retina breakdown by the RPE disintegration shown by fluorescence angiography coincide very closely, hence the occurrence of microbubbles can be taken as a proof of successful RPE damage [63,64]. Fortunately, microbubble formation and their dynamics can indirectly and non-invasively be measured in vivo during irradiation by different methods:…”

“…11.7 shows the applied energy ramp and c Fig. 11.7 Pulse energy ramp for a SRT spot (a) with acoustical (b) and optical transients (c) color-coded for the same laser spot, exemplary from a clinical trial using both techniques simultaneously [64]. Blue colours represent sub MBF energies.…”

“…In case of an automated feedback, laser emission should be ceased when reaching the green or orange pulses to safely stay within the therapeutic window in order to prevent large thermomechanical disruption. This can lead to collateral damage, including bleeding as it has been observed after therapeutic 3 ns laser exposure [62] the according transients recorded during a clinical study at the University eye clinics in Kiel (UKSH) and Hannover (MHH) [64].…”